Chang Der-Ming
Department of Bioindustry Technology, Da Yeh University, 112 Shan Jiau Rd, Da Tsuen, Changhua 515, Taiwan, ROC.
Biotechnol Prog. 2003 May-Jun;19(3):1064-70. doi: 10.1021/bp025792a.
The bioreactor will play an important role in future biological manufacturing. For economic profit, important profiles of the feed rate in fed-batch cultures have been discussed. Unfortunately, the optimal feed rate is less robust. In these studies there exists the snowball effect in a substrate-inhibited bioprocess, in which substrate is accumulated due to uncertain parameters in the model or feed-rate error. The snowball effect also exists in multi-substrate-limited processes. In further studies, the interaction between the substrates has been higher in essential substrates than in growth-enhancing substrates. In a typical fed-batch bioreactor, the amount of the product can be reduced to 1% or less when the snowball effect arises. A new control structure, i.e., an off-line optimized feedforward controller added to a gain-scheduling PI(2)D feedback controller, is proposed to eliminate the troublesome snowball effect. The proposed control strategy recovers the yield up to 95%. Moreover, the robustness of the proposed control structure is demonstrated by simulation.
生物反应器将在未来的生物制造中发挥重要作用。出于经济利益考虑，已讨论了分批补料培养中补料速率的重要特征。不幸的是，最佳补料速率的稳健性较差。在这些研究中，底物抑制生物过程中存在雪球效应，其中由于模型中的不确定参数或补料速率误差导致底物积累。多底物限制过程中也存在雪球效应。在进一步的研究中，必需底物之间的相互作用比生长促进底物之间的相互作用更强。在典型的分批补料生物反应器中，当出现雪球效应时，产物量可降至1%或更低。提出了一种新的控制结构，即在增益调度PI(2)D反馈控制器中添加离线优化前馈控制器，以消除麻烦的雪球效应。所提出的控制策略可将产率恢复至95%。此外，通过仿真证明了所提出控制结构的稳健性。
